Sensors for 3-hydroxybutyrate detection

Abstract

The invention provides amperometric analyte sensor systems comprising one or more electrodes designed to monitor in vivo levels of 3-hydroxybutyrate (and optionally glucose as well) in order to facilitate the management of diabetic ketoacidosis. The invention further includes compositions, elements and methods useful with such amperometric analyte sensor systems.

1 . A method of making an amperometric analyte sensor electrode that estimates concentrations of 3-hydroxybutyrate comprising the steps of:
 forming a 3-hydroxybutyrate detecting electrode by:   providing a base layer;   forming conductive layer on the base layer, wherein the conductive layer includes an electroactive material;   operatively coupling a 3-hydroxybutyrate dehydrogenase, a mediator and nicotinamide adenine dinucleotide to the electroactive material; and   forming an analyte modulating layer disposed over the electroactive material, wherein the analyte modulating layer includes a composition that modulates the diffusion of 3-hydroxybutyrate therethrough; and   (c) forming a contact pad for connecting an electrical conduit to the 3-hydroxybutyrate sensing electrode;   so that the amperometric analyte sensor electrode is made.   
     
     
         2 . The method of  claim 1 , wherein an analyte modulating layer comprises:
 a polyurethane/polyurea polymer;   a branched acrylate polymer;   a cellulose acetate polymer; or   a poly-2-hydroxyethyl methacrylate polymer.   
     
     
         3 . The method of  claim 1 , wherein the 3-hydroxybutyrate electrode is further coated with at least one further layer of material comprising:
 an interference rejection layer;   a protein layer; and   an adhesion promoting layer; and   a layer comprising poly-1-lysine polymers having molecular weights between 30 KDa and 300 KDa.   
     
     
         4 . The method of  claim 1 , further comprising disposing the 3-hydroxybutyrate sensing electrode within a piercing member. 
     
     
         5 . A method of making an amperometric analyte sensor that estimates a concentration of glucose and a concentration of 3-hydroxybutyrate comprising the steps of:
 (a) forming a glucose detecting electrode by:   providing a base layer;   forming conductive layer on the base layer, wherein the conductive layer includes an electroactive material;   forming an analyte sensing layer over the working electrode, wherein the analyte sensing layer comprises glucose oxidase; and   forming an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer includes a composition that modulates the diffusion of glucose therethrough; and   (b) forming a 3-hydroxybutyrate detecting electrode by:   providing a base layer;   forming conductive layer on the base layer, wherein the conductive layer includes an electroactive material;   forming an analyte sensing layer over the working electrode, wherein the analyte sensing layer comprises 3-hydroxybutyrate dehydrogenase and nicotinamide adenine dinucleotide; and   forming an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer includes a composition that modulates the diffusion of 3-hydroxybutyrate therethrough; and   (c) forming a contact pad for connecting an electrical conduit to the glucose sensing electrode and the 3-hydroxybutyrate sensing electrode;   so that the amperometric analyte sensor is made.